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Lysine-specific demethylase 1 regulates differentiation onset and migration of trophoblast stem cells

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  • Dongmei Zhu

    (Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg)

  • Stefanie Hölz

    (Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg)

  • Eric Metzger

    (Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg)

  • Mihael Pavlovic

    (Medizinische Universitätsklinik, Nephrologie, Klinikum der Universität Freiburg)

  • Anett Jandausch

    (Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg)

  • Cordula Jilg

    (Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg)

  • Petra Galgoczy

    (Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg)

  • Corinna Herz

    (Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg)

  • Markus Moser

    (Max Planck Institute of Biochemistry)

  • Daniel Metzger

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire)

  • Thomas Günther

    (Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg)

  • Sebastian J. Arnold

    (Medizinische Universitätsklinik, Nephrologie, Klinikum der Universität Freiburg
    BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs-University)

  • Roland Schüle

    (Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg
    BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs-University)

Abstract

Propagation and differentiation of stem cell populations are tightly regulated to provide sufficient cell numbers for tissue formation while maintaining the stem cell pool. Embryonic parts of the mammalian placenta are generated from differentiating trophoblast stem cells (TSCs) invading the maternal decidua. Here we demonstrate that lysine-specific demethylase 1 (Lsd1) regulates differentiation onset of TSCs. Deletion of Lsd1 in mice results in the reduction of TSC number, diminished formation of trophectoderm tissues and early embryonic lethality. Lsd1-deficient TSCs display features of differentiation initiation, including alterations of cell morphology, and increased migration and invasion. We show that increased TSC motility is mediated by the premature expression of the transcription factor Ovol2 that is directly repressed by Lsd1 in undifferentiated cells. In summary, our data demonstrate that the epigenetic modifier Lsd1 functions as a gatekeeper for the differentiation onset of TSCs, whereby differentiation-associated cell migration is controlled by the transcription factor Ovol2.

Suggested Citation

  • Dongmei Zhu & Stefanie Hölz & Eric Metzger & Mihael Pavlovic & Anett Jandausch & Cordula Jilg & Petra Galgoczy & Corinna Herz & Markus Moser & Daniel Metzger & Thomas Günther & Sebastian J. Arnold & R, 2014. "Lysine-specific demethylase 1 regulates differentiation onset and migration of trophoblast stem cells," Nature Communications, Nature, vol. 5(1), pages 1-14, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4174
    DOI: 10.1038/ncomms4174
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    Cited by:

    1. Qingshuang Cai & Rajesh Sahu & Vanessa Ueberschlag-Pitiot & Sirine Souali-Crespo & Céline Charvet & Ilyes Silem & Félicie Cottard & Tao Ye & Fatima Taleb & Eric Metzger & Roland Schuele & Isabelle M. , 2024. "LSD1 inhibition circumvents glucocorticoid-induced muscle wasting of male mice," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Xue Zhong & Nagesh Peddada & Jianhui Wang & James J. Moresco & Xiaowei Zhan & John M. Shelton & Jeffrey A. SoRelle & Katie Keller & Danielle Renee Lazaro & Eva Marie Y. Moresco & Jin Huk Choi & Bruce , 2023. "OVOL2 sustains postnatal thymic epithelial cell identity," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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